Low expression of CD112 is associated with poor overall survival in patients with hepatocellular carcinoma

CD112 as an important ligand of CD226 can stimulate the natural killer (NK) cell mediated target cell lysis. Previous studies have reported that CD112 is involved in cancer initiation and progression. However, its expression and clinical significance in hepatocellular carcinoma (HCC) have never been investigated. In this study, we used immunohistochemistry to examine CD112 expression in cancer and pericancer tissues from 159 HCC cases. Western blot and immunofluorescence were used to detect CD112 expression in HCC cell lines. chi(2) Test was used to assess the association of CD112 expression with clinicopathological characteristics, whereas Kaplan-Meier survival function and Cox proportional hazards regression model were used to explore the association between CD112 expression and clinical outcome of patients with HCC. Overall, CD112 expression was significantly reduced in HCC tissues when compared with adjacent pericanber liver tissues (P < .001). Western blot and immunofluorescence analyses showed. that most HCC cell lines had low CD112 expression level. Furthermore, low CD112 expression was significantly associated with high serum alpha-fetoprotein level (P = .004) in patients with HCC. Kaplan-Meier analysis showed that patients with low CD112 expression had poorer postsurgery overall survival than those with high CD112 expression (log-rank P = .045). In conclusion, our findings demonstrate that the down-regulation of CD112 may be an important mechanism through which HCC cells evade the natural killer cell mediated immunosurveillance, and thus, CD112 may be a useful biomarker to assess the immunologic niche of HCC. (C) 2014 Elsevier Inc. All rights reserved.